Estimating changes in antibiotic consumption in the USA with the introduction of doxycycline post-exposure prophylaxis
Authors: Kirstin I Oliveira Roster, Yonatan H Grad
Journal: The Lancet Microbe (2023)

Doxycycline as a post-exposure prophylaxis (doxy-PEP) reduced the risk of bacterial sexually transmitted infections (STIs) in a randomised controlled trial of men who have sex with men taking HIV pre-exposure prophylaxis (PrEP), transgender women taking HIV PrEP, and people living with HIV.1Luetkemeyer AF Donnell D Dombrowski JC et al.Postexposure doxycycline to prevent bacterial sexually transmitted infections.N Engl J Med. 2023; 388: 1296-1306Crossref PubMed Scopus (20) Google Scholar There is concern that increased consumption of doxycycline might increase antimicrobial resistance, including doxycycline-resistant Neisseria gonorrhoeae, Staphylococcus aureus, and Streptococcus pneumoniae.2Mortimer TD Grad YH A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on Neisseria gonorrhoeae antimicrobial resistance.Clin Infect Dis. 2023; 77: 788-791Crossref PubMed Scopus (2) Google Scholar, 3Whiley DM Tickner JA Kundu RL Hogan TR van Hal SJ Lahra MM Selection of Neisseria gonorrhoeae ceftriaxone resistance using doxycycline post-exposure prophylaxis.Lancet Infect Dis. 2023; 23: e268-e269Summary Full Text Full Text PDF PubMed Google Scholar, 4Kong FYS Kenyon C Unemo M Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections.J Antimicrob Chemother. 2023; 78: 1561-1568Crossref PubMed Scopus (0) Google Scholar Antibiotic use might change with the introduction of doxy-PEP; estimating this change could inform considerations of the risks of antimicrobial resistance and the benefits of STI prevention. We estimated the first-order expected increase in antibiotic consumption in the USA under several doxy-PEP prescribing scenarios (appendix pp 1–2). We accounted for defined daily doses, hereafter referred to as doses, of antibiotics that could be averted due to the prevention of chlamydia (doxycycline), gonorrhoea (ceftriaxone), and syphilis (penicillin) infections by doxy-PEP, with rates of consumption (ie, four doses per person-month) and relative risk estimates as reported in the DoxyPEP trial (appendix p 5).1Luetkemeyer AF Donnell D Dombrowski JC et al.Postexposure doxycycline to prevent bacterial sexually transmitted infections.N Engl J Med. 2023; 388: 1296-1306Crossref PubMed Scopus (20) Google Scholar We estimated that 0·86 million people in the USA might be eligible for doxy-PEP under the enrolment criteria of the DoxyPEP trial (ie, up to an estimated 0·53 million people living with HIV and up to an estimated 0·33 million people currently taking HIV PrEP; appendix p 5); however, we did not include their requirement of an STI in the past year.1Luetkemeyer AF Donnell D Dombrowski JC et al.Postexposure doxycycline to prevent bacterial sexually transmitted infections.N Engl J Med. 2023; 388: 1296-1306Crossref PubMed Scopus (20) Google Scholar If 75% of people in this population began to take doxy-PEP, monthly antibiotic consumption would increase by approximately 2·52 million doses (ie, doxy-PEP consumption of 2·58 million doses minus 62 100 antibiotic doses that would otherwise have been used for bacterial STI treatment; appendix p 6). If the entire eligible population began to take doxy-PEP, monthly antibiotic consumption would be expected to increase by 3·36 million doses (appendix p 7). A retrospective analysis of ten prescribing strategies based on the PrEP use, HIV status, and bacterial STI history of people predicted substantial variation across the strategies in the number of infections averted per person taking doxy-PEP.5Traeger MW Mayer KH Krakower DS Gitin S Jenness SM Marcus JL Potential impact of doxycycline post-exposure prophylaxis prescribing strategies on incidence of bacterial sexually transmitted infections.Clin Infect Dis. 2023; (published online Aug 18.)https://doi.org/10.1093/cid/ciad488Crossref PubMed Google Scholar The prescribing strategy with the lowest number needed to treat to prevent a chlamydia infection was a diagnosis of two bacterial STIs within a 6-month period. 75% implementation of this strategy among men who have sex with men taking HIV PrEP and people living with HIV would lead to an increase in monthly antibiotic consumption of 0·28 million doses in the USA, whereas widespread (ie, 100%) implementation would lead to an increase of 0·37 million doses (appendix p 7). Among bacterial STI history-based prescribing strategies, the increase in antibiotic consumption was directly related to the size of the treated population;5Traeger MW Mayer KH Krakower DS Gitin S Jenness SM Marcus JL Potential impact of doxycycline post-exposure prophylaxis prescribing strategies on incidence of bacterial sexually transmitted infections.Clin Infect Dis. 2023; (published online Aug 18.)https://doi.org/10.1093/cid/ciad488Crossref PubMed Google Scholar prescribing doxy-PEP to individuals with a diagnosis of at least two concurrent bacterial STIs would be expected to result in the smallest population treated and an increase in antibiotic consumption (ie, 0·18 million monthly doses with 75% implementation and 0·24 million monthly doses with 100% implementation; appendix pp 2, 7). Fully balancing doxy-PEP consumption with the number of averted doxycycline doses for chlamydia treatment would require restricting prescriptions to a group with an incidence of 7·8 infections per person-year while maintaining similar levels of monthly doxy-PEP consumption and reductions in chlamydia infection risk as reported for people taking HIV PrEP (appendix p 3). These estimates suggest that doxycycline consumption in the USA will increase with the introduction of doxy-PEP, even when accounting for the reduction in antibiotics used to treat chlamydia, gonorrhoea, and syphilis; the extent of this increase will depend on the size of the population taking doxy-PEP. Monitoring changes in antibiotic consumption, disease incidence, and burden of resistance will be important to understand the effects of doxy-PEP. This work was supported by the US National Institute of Allergy and Infectious Diseases (grant numbers R01 AI132606 and R01 AI153521) and the US Centers for Disease Control and Prevention (contract number 200–2016–91779), paid to YHG. The findings, conclusions, and views expressed are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. KIOR declares no competing interests. Download .pdf (.29 MB) Help with pdf files Supplementary appendix